Nanotechnology applications are being incorporated into our daily lives, but the safety of nanomaterials usage still awaits thorough assessment. Currently, little is known about nanomaterial-biological interactions, and to bridge this gap, I propose using embryonic zebrafish as a rapid, in vivo system to investigate the activity of nanomaterials at the molecular level. High-purity, ligand-functionalized silver nanoparticles (AgNPs) can be precisely engineered to custom-manipulate physicochemical properties. I hypothesize that the biological activity of nanomaterials is dependent upon primary particle size, size distribution, chemical composition of surface groups, surface charge and state of agglomeration. To test this hypothesis, I will collect toxicity data including morbidity and mortality dose response, uptake concentration, and nanoparticle exposure-induced changes in gene expression. Additionally, by exposing embryonic zebrafish to silver nanoparticles (AgNPs) engineered to exhibit highly specific physicochemical properties, I will define which properties are responsible for causing specific biological effects. All data will be recorded in the Nanomaterial-Biological Interactions (NBI) knowledge base. The NBI knowledgebase serves as a warehouse for annotated data on nanomaterial characterization, synthesis methods, and nanomaterial-biological interactions defined at multiple levels of biological organization. The data I submit to the NBI knowledgebase will facilitate identification of key data for predicting the biological effects of nanomaterial exposure based on physicochemical properties.